Sixteen
monoclonal antibodies that were obtained after immunization of BALB/c mice with intact
melanoma cells or extracts of
melanoma cells were tested for reactivity with normal and malignant melanocytic cells in situ, using an immunoperoxidase technique on frozen tissue sections. Sections representing six histopathologically defined stages of
tumor progression, ranging from normal melanocytes to highly malignant metastatic lesions, were used. Thirteen
monoclonal antibodies (MAbs) did not
stain normal melanocytes in situ, whereas three MAbs weakly stained between 1 and 12.5% of melanocytes in 6-22% of the skin sections examined. MAb B 73.1, which was produced by immunization of mice with human natural killer cells and which binds to the
Fc receptor of natural killer cells and granulocytes, reacted exclusively with malignant cells that represent the last two stages of
tumor progression, vertical growth phase (VGP) primary
melanoma and metastatic
melanoma. All other
antibodies showed variable reactivity with benign proliferative lesions or radial growth phase (RGP), an early stage of primary
melanoma. Staining by MAbs that were reactive with
gangliosides, unknown
antigens, receptors, and two
proteins (120/94 kDa
protein and 250 kDa
glycoprotein) showed a gradual increase in subsequent stages of
tumor progression. Two steps in
tumor progression were characterized by significant quantitative changes in the expression of
antigens detected by the MAbs used in this study. First, mature
nevus cells showed significantly higher reactivity with a panel of six MAbs, when compared to normal melanocytes. Second, a separate panel of six MAbs discriminated between RGP and VGP primary
melanoma cells. No significant differences in
antigen expression were found between
dysplastic nevus cells and RGP
melanoma, except that some
antigens (
nerve growth factor receptor and GD2/GD3
gangliosides) appear to be expressed at lower levels in RGP lesions, nor did VGP primary and metastatic
melanomas show significant differences in
antigen expression. These results suggest that (a)
tumor progression of melanocytic cells in vivo is accompanied by significant quantitative differences in the expression of
antigens, (b) some of the
antigens examined here are associated with biologically aggressive malignant lesions but not normal or premalignant melanocytic cells, and (c) RGP primary
melanoma cells are antigenically more similar to
nevus cells than to VGP primary
melanoma cells.